TiO2 nanoparticles induced hippocampal neuroinflammation in mice

• Published in: PloS one 2014-03, Vol.9 (3), p.e92230
• Main Authors: Ze, Yuguan, Sheng, Lei, Zhao, Xiaoyang, Hong, Jie, Ze, Xiao, Yu, Xiaohong, Pan, Xiaoyu, Lin, Anan, Zhao, Yue, Zhang, Chi, Zhou, Qiuping, Wang, Ling, Hong, Fashui
• Format: Article
• Language: English
• Subjects: Animals; Attention; Biocompatibility; Biology and Life Sciences; Biomedical materials; Body weight; Brain; Brain research; Carbon black; Central nervous system; Cytokines - biosynthesis; Engineering and Technology; Exposure; Female; Food industry; Food processing industry; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; I-kappa B Kinase - metabolism; I-kappa B Proteins - metabolism; Immune system; Industrial areas; Inflammation; Inflammation - chemically induced; Interleukin 2; Kinases; Laboratory animals; Maze Learning - drug effects; Medicine and Health Sciences; Memory tasks; Mice; Motor Activity - drug effects; Nanoparticles; NF-kappa B - metabolism; NF-kappa B p52 Subunit - metabolism; NF-κB protein; Physical Sciences; Proteins; Receptors; Research and Analysis Methods; Rodents; Signal transduction; Signaling; Spatial analysis; Spatial memory; Stem cells; Surgical implants; Titanium; Titanium - pharmacology; Titanium dioxide; TLR2 protein; TLR4 protein; Toll-Like Receptor 2 - drug effects; Toll-Like Receptor 2 - physiology; Toll-Like Receptor 4 - drug effects; Toll-Like Receptor 4 - physiology; Toll-like receptors; Toll-Like Receptors - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092230

Titanium dioxide nanoparticles (TiO2 NPs) have been used in various medical and industrial areas. However, the impacts of these nanoparticles on neuroinflammation in the brain are poorly understood. In this study, mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days, and the TLRs/TNF-α/NF-κB signaling pathway associated with the hippocampal neuroinflammation was investigated. Our findings showed titanium accumulation in the hippocampus, neuroinflammation and impairment of spatial memory in mice following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly activated the expression of Toll-like receptors (TLR2, TLR4), tumor necrosis factor-α, nucleic IκB kinase, NF-κB-inducible kinase, nucleic factor-κB, NF-κB2(p52), RelA(p65), and significantly suppressed the expression of IκB and interleukin-2. These findings suggest that neuroinflammation may be involved in TiO2 NP-induced alterations of cytokine expression in mouse hippocampus. Therefore, more attention should be focused on the application of TiO2 NPs in the food industry and their long-term exposure effects, especially in the human central nervous system.